Katsuhisa Omagari

Fatty liver in non-alcoholic non-overweight Japanese adults: Incidence and clinical characteristics

Background and Aims: Fatty liver is not uncommon in many countries, including Japan, and is mainly caused by alcohol usage and obesity. The aim of this study was to determine the incidence and causative factors of fatty liver in Japanese adults.

Ghrelin enhances gastric motility through direct stimulation of intrinsic neural pathways and capsaicin-sensitive afferent neurones in rats

Background: Ghrelin may stimulate gastric motility via the vagal nerve pathway. However, the mechanism of ghrelin-induced changes in gastrointestinal motility has not yet been clearly defined. The present study was designed to investigate whether ghrelin accelerates gastric emptying via capsaicin-sensitive afferent neurones and directly affects the enteric neuromuscular function. Methods: Gastric emptying of nutrient solids was assessed after intravenous administration of saline or ghrelin in conscious rats. The effects of ghrelin on gastric emptying were also examined in rats pretreated with capsaicin. Gastric emptying and intestinal transit of non-caloric liquids were evaluated using [Formula: See Text]Cr solution. The effects of ghrelin on spontaneous contractile activities of isolated strips from stomach and jejunum were also investigated and the influence of ghrelin on motor responses to carbachol and electrical field stimulation was examined. Results: Ghrelin significantly accelerated gastric emptying of both nutrient solids and non-caloric liquids in conscious rats. The intestinal transit of non-caloric liquids was also enhanced by ghrelin. Pretreatment with capsaicin prevented the ghrelin-induced acceleration of gastric emptying of nutrient solids. Ghrelin did not modulate spontaneous and carbachol-induced contractions of strips of gastric body, gastric antrum and jejunum. However, electrical field stimulation-induced contractions were significantly enhanced by ghrelin in the gastric body. Conclusions: The results suggest that the stimulatory effects of ghrelin on gastric motility are mediated by direct stimulation of the enteric neural pathway and capsaicin-sensitive afferent neurones.

Elevated levels of chemokines in esophageal mucosa of patients with reflux esophagitis.

Abstract Objective Chemokines play a key role in the pathogenesis of various inflammatory conditions. However, there is little information on their profile in reflux esophagitis (RE). We sought to study esophageal mucosa levels of chemokines in RE. Methods A total of 32 outpatients with RE and 13 normal controls were studied. Endoscopic severity of RE was classified according to the Los Angeles grading system. Paired biopsy specimens were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap frozen for measurement of mucosal levels of interleukin 8 (IL-8), monocyte chemoattractant protein 1 (MCP-1), regulated on activation normal T-cell expressed and presumably secreted (RANTES), and IL-1β by enzyme linked immunosorbent assays, while the other was formalin-fixed for histopathological evaluation. Results IL-8, MCP-1, and RANTES levels were significantly higher in esophageal mucosa of RE patients than those of the controls. IL-8 levels correlated significantly with the endoscopic severity of RE. Basal zone hyperplasia and papillary elongation, histopathological hallmarks of RE, were both associated with higher levels of IL-8 and MCP-1. The presence of intraepithelial neutrophils and eosinophils, which also indicate RE, was associated with high levels of IL-8 and RANTES, respectively. There were no significant differences in IL-1β levels between the RE and control groups, but IL-1β levels correlated significantly with the IL-8 production. Again, the IL-8 levels were significantly decreased after lansoprazole treatment. Conclusion Our results indicate that chemokines produced locally in the esophageal mucosa may be involved in the development and progression of RE.

Enhanced Expression of Interleukin-8 and Activation of Nuclear Factor Kappa-B in Endoscopy-negative Gastroesophageal Reflux Disease

OBJECTIVE:Interleukin-8 (IL-8) mediates neutrophil trafficking via its receptors. Recent studies have shown that IL-8 is likely involved in the development and progression of erosive reflux esophagitis (RE), yet little is known about its implication in endoscopy-negative gastroesophageal reflux disease (GERD). The purpose of this study was to determine IL-8 messenger ribonucleic acid (mRNA) expression levels in endoscopy-negative GERD, along with assessment of nuclear factor kappaB (NF-κB) activation, which upregulates IL-8 expression.METHODS:We studied 31 patients with endoscopy-negative GERD, 15 patients with erosive RE, and 15 asymptomatic controls. Paired biopsy samples were taken from the esophagus 3 cm above the gastroesophageal junction; one biopsy was snap-frozen for measurement of IL-8 mRNA levels by real-time quantitative polymerase chain reaction, and another was formalin-fixed for histopathological evaluation. In nine endoscopy-negative GERD patients, the IL-8 mRNA expression levels were measured before and 8 wk after treatment with lansoprazole. We also sampled additional specimens for NF-κB-DNA binding assay and immunohistochemical analyses of NF-κB p65 and p50 subunits, IL-8 and specific IL-8 receptor, CXCR-1.RESULTS:The relative IL-8 mRNA expression levels were significantly higher in esophageal mucosa of patients with endoscopy-negative GERD than those of the controls. The presence of basal zone hyperplasia and intraepithelial neutrophils, histopathological hallmarks of GERD, were associated with higher levels of IL-8 mRNA. Lansoprazole treatment significantly reduced the IL-8 mRNA expression levels. The esophageal epithelium of patients with GERD showed intense immunoreactivity for IL-8, and expressed CXCR-1 antigen. We found NF-κB activation in esophageal mucosa in GERD patients and the NF-κB subunits were localized predominantly in the nuclei of IL-8-expressing cells.CONCLUSIONS:Our results demonstrate enhanced mucosal expression of IL-8 in incipient GERD even without mucosal breaks. NF-κB activation may be implicated in the pathogenesis in GERD.

Implication of NF-kappaB in Helicobacter pylori-associated gastritis

OBJECTIVE:Transcription factor NF-κB plays a pivotal role in inflammatory responses by up-regulating mRNA expression of bioactive molecules such as chemokines and adhesion molecules. The present study was designed to elucidate the implication of NF-κB in Helicobacter pylori–associated gastritis (HAG).METHODS:We examined 41 patients with HAG and 18 H. pylori–negative control subjects. Expression of activated NF-κB was studied in situ by immunohistochemistry using α-p65 mouse monoclonal antibody (α-p65 mAb), which recognizes activated NF-κB. To identify the cell types in which NF-κB was activated, we performed immunohistochemical analysis using antibodies against vascular endothelial cells, macrophages, and B and T lymphocytes. We also examined the colocalization of activated NF-κB with the expression of intercellular adhesion molecule-1 (ICAM-1) on endothelial cells. We measured the levels of NF-κB–dependent chemokines including interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1), regulated on activation normal T-cell expressed and secreted (RANTES) and macrophage inflammatory protein-1α (MIP-1α) in antral mucosa by ELISA (ELISA).RESULTS:Activated NF-κB was detected in the nuclei of epithelial cells in antral mucosa, especially of patients with HAG. NF-κB positivity index (NF-κB PI), representing the percentages of epithelial cells with positive nuclear staining for activated NF-κB, was significantly higher in patients with HAG than in H. pylori–negative controls. NF-κB PI correlated significantly with histological scores of gastritis. Moreover, activated NF-κB was identified in the nuclei of vascular endothelial cells, macrophages, and B lymphocytes within the lamina propria in HAG. Colocalization of activated NF-κB with ICAM-1 expression in the same endothelial cells was demonstrated. The IL-8 levels significantly correlated with the NF-κB PI.CONCLUSIONS:In addition to epithelial cells, macrophages, vascular endothelial cells, and B lymphocytes contained activated NF-κB. In these cells, activated NF-κB may be involved in the inflammation process in HAG through the up-regulation of chemokines or adhesion molecules.

Recent insights into digestive motility in functional dyspepsia

Functional gastrointestinal disorders, such as functional dyspepsia (FD) and irritable bowel syndrome, are common pathologies of the gut. FD is a clinical syndrome defined as chronic or recurrent pain or discomfort of unknown origin in the upper abdomen. The pathophysiological mechanisms responsible for FD have not been fully elucidated, but new ideas regarding its pathophysiology and the significance of the pathophysiology with respect to the symptom pattern of FD have emerged. In particular, there is growing interest in alterations in gastric motility, such as accommodation to a meal or gastric emptying, and visceral sensation in FD. The mechanisms underlying impaired gastroduodenal motor function are unclear, but possible factors include abnormal neurohormonal function, autonomic dysfunction, visceral hypersensitivity to acid or mechanical distention, Helicobacter pylori infection, acute gastrointestinal infection, psychosocial comorbidity, and stress. Although the optimum treatment for FD is not yet clearly established, acid-suppressive drugs, prokinetic agents, eradication of H. pylori, and antidepressants have been widely used in the management of patients with FD. The therapeutic efficacy of prokinetics such as itopride hydrochloride and mosapride citrate in the treatment of FD is supported by the results of relatively large and well-controlled studies. In addition, recent research has yielded new therapeutic agents and modalities for dysmotility in FD, including agonists/antagonists of various sensorimotor receptors, activation of the nitrergic pathway, kampo medicine, acupuncture, and gastric electric stimulation. This review discusses recent research on the pathophysiology of and treatment options for FD, with special attention given to digestive dysmotility.

High‐dose rabeprazole–amoxicillin versus rabeprazole–amoxicillin–metronidazole as second‐line treatment after failure of the Japanese standard regimen for Helicobacter pylori infection

Background : There is currently no optimal second‐line treatment after failure of Helicobacter pylori triple therapy.

Clinicopathological study of nonalcoholic fatty liver disease in Japan: the risk factors for fibrosis.

Background/Aims: We evaluated patients with nonalcoholic fatty liver disease (NAFLD) and compared the clinical and pathological features to identify the risk factors for NAFLD with severe fibrosis.

Relation among plasma ghrelin level, gastric emptying, and psychologic condition in patients with functional dyspepsia.

Background and Goals Neurohormonal factors might play a role in the pathogenesis of functional dyspepsia (FD). However, the role of ghrelin, a gastrointestinal hormone that stimulates gastric motility, in FD is not yet clearly defined. The present study was designed to investigate plasma ghrelin levels and their relation with gastric emptying and psychologic status in FD. Methods Sixteen patients with FD of the dysmotility type and 19 healthy controls were enrolled in the study. Plasma active and desacyl ghrelin concentrations before and after test meal were measured by enzyme-linked immunosorbent assay. Gastric emptying and psychologic condition were studied using 13C acetate breath test and questionnaires, respectively. Results Gastric emptying was significantly prolonged in patients with FD compared with controls. Fasting desacyl and total ghrelin levels were significantly lower in FD patients than in controls, but fasting active ghrelin levels and postprandial levels of ghrelin in both forms were similar between the 2 groups. Fasting total ghrelin levels in FD patients did not differ from the postprandial levels, in contrast to what was found for controls. There was no significant association among gastric emptying, plasma ghrelin levels, and psychologic factors in FD patients. Conclusions Total secretory ability or metabolic condition of ghrelin may be altered in patients with FD. This seems to play a role in the pathophysiology of dysmotility type FD, independent of delayed gastric emptying or psychologic disorders.

Preliminary analysis of a newly proposed prognostic scoring system (SLiDe score) for hepatocellular carcinoma

Background:  The long‐term prognosis of hepatocellular carcinoma (HCC) remains poor and the prediction of survival is often difficult because of the limited liver function and frequent recurrence of HCC in most patients. Therefore, a prognostic classification of HCC should account for both tumor‐related variables and liver function.